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DOI: 10.1055/s-2001-15032
Verminderte Plättchenaggregation bei ACE-Hemmertherapie
Ergebnisse einer PilotstudieDecreased platelet aggregation with angiotensin converting enzyme inhibitor medication: results of a pilot studyPublication History
Publication Date:
31 December 2001 (online)
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Hintergrund und Fragestellung: Plaqueruptur und konsekutive Thrombose sind Schlüsselereignisse bei Komplikation und Progression atherosklerotischer Organleiden. Kürzlich konnte die HOPE-Studie eine signifikante Verminderung kardiovaskulärer Ereignisse für den Angiotensin Converting Enzyme (ACE) -Hemmer Ramipril zeigen. Zur Evaluation des therapeutischen Potenzials dieser Substanzklasse wurde in der vorliegenden Studie koagulatorische Aktivität bei kardiovaskulären Patienten mit ACE-Hemmertherapie untersucht und diese mit der von unbehandelten Kontrollpatienten bzw. mit der von Patienten mit Acetylsalicylsäure (ASS)-Therapie verglichen.
Patienten und Methodik: Proben von insgesamt 204 Patienten mit koronarer Herzerkrankung und/oder arterieller Hypertonie wurden mittels Vollblutaggregometrie analysiert. Dabei war die Agonisten-induzierte Plättchenaggregation (Kollagen, ADP) durch die Zunahme der Impedanz (in Ohm) quantifiziert. Diese Daten wurden mit Vorliegen bzw. Fehlen einer ACE-Hemmer- bzw. ASS-Medikation korreliert. Analog wurden die koagulatorischen Potenziale bei Therapie mit Beta-Blockern, Calcium-Antagonisten, CSE-Hemmern und Nitraten evaluiert.
Ergebnisse: Als zentraler Befund war die Plättchenaggregation bei Studienteilnehmern mit ACE-Hemmer-Einnahme gegenüber der unbehandelter Kontrollpatienten vermindert, ausgewiesen durch eine signifikant verminderte Zunahme der Impedanz. Die Kollagen-induzierte Plättchenaggregation wurde um 18 % (p = 0,025), die ADP-induzierte um 39 % (p = 0,039) gehemmt. Bei ASS-Medikation nahm die Kollagen-induzierte Plättchenaggregation durchschnittlich um 20 % (p = 0,020) ab; Effekte nach Induktion mit ADP waren nicht signifikant. Bei kombinierter Therapie mit ACE-Hemmern und ASS war ein ausgeprägter antithrombozytärer Effekt nach Kollagen-Induktion beobachtbar; die Plättchenaggregation nahm um 26 % (p = 0,003) ab. Beta-Blocker, Calcium-Antagonisten, CSE-Hemmer und Nitrate zeigten keinen signifikanten Einfluss auf die Plättchenaggregation.
Folgerungen: ACE-Hemmer-Therapie führt zu einer signifikanten Verminderung der Plättchenaggregation, die ex vivo mit Hilfe der Vollblut-Aggregometrie messbar und quantifizierbar wird. Neben bereits bekannten Wirkungen dieser Substanzklasse, insbesondere auf Endothel und Fibrinolyse, könnten antithrombozytäre Effekte die günstige Beeinflussung klinisch relevanter kardiovaskulärer Ereignisse zusätzlich erklären.
Decreased platelet aggregation with angiotensin converting enzyme inhibitor medication: results of a pilot study
Background and objective: Plaque rupture and subsequent thrombosis are key events in the complication and progression of atherosclerotic disease. Recently, the HOPE study showed a significant decrease in cardiovascular complications with the angiotensin converting enzyme (ACE) inhibitor (ramipril). To assess the therapeutic potential of this drug class, the present study evaluates the coagulative activity in cardiovascular patients with ACE inhibitors and compares these data with those of untreated patients and with those of patients taking aspirin, resp.
Methods: Blood samples from 204 patients with coronary heart disease and/or arterial hypertension were analyzed by whole-blood lumi-aggregometry. Platelet aggregation was determined by the increase in impedance across paired electrodes in response to the stimulatory agents collagen and ADP, respectively. The data were correlated with the presence or absence of ACE inhibitor and/or aspirin medication. Analogously, the coagulative potential of beta-blockers, calcium antagonists, CSE-inhibitors and nitrates were studied.
Results: As the central finding, study participants treated with ACE inhibitors showed a decreased platelet aggregation compared to untreated control patients, indicated by a significantly reduced increase in impedance. Platelet aggregation induced by collagen decreased by 18 % (p = 0.025), that induced by ADP by 39 % (p = 0.039). With aspirin medication, the collagen-induced decrease amounted to 20 % (p = 0.020); no significant effect was seen by ADP stimulation. With combined intake of ACE inhibitors and aspirin, collagen-induced platelet aggregation was found markedly reduced. Platelet aggregation decreased by 26 % (p = 0.003). Beta-blockers, calcium antagonists, CSE inhibitors and nitrates did not reveal a significant influence on platelet aggregation.
Conclusions: ACE inhibition decreases platelet aggregation, as detected and quantified by ex vivo whole-blood aggregometry. Beyond known effects of this drug class, in particular on endothelium and fibrinolysis, antithrombotic effects may explain the positive influence on major clinical cardiovascular events.
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Korrespondenz
Prof. Dr. Gerhard Bauriedel
Medizinische Klinik und Poliklinik II Universitätsklinikum
Bonn
Sigmund-Freud-Straße 25
53105 Bonn
Phone: 0228/287-6670
Fax: 0228/287-4323
Email: Gerhard.Bauriedel@ukb.uni-bonn.de